AVIANDISEASES45:437-441, 2001

Research NoteA Novel Delivery of Oxytetracycline in Turkey Breeder Hens D. K. Carver,AJ. L. Grimes,A V. L. Christensen,A K. A. Joyce,B B. D. Fairchild,A and A. S. FairchildA ADepartment of Poultry Science, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27695 BBlue Ridge Pharmaceuticals, Inc., Greensboro, NC 27410 Received 8 November 1999

SUMMARY. A novel product (SQ12) for subcutaneous (SQ) injectable delivery of oxytetracycline (OTC) has been developed for use in livestock. SQ12 employs microfluidic spheres encasing OTC crystals, which allows for longer release of the OTC compared with other injectable antibiotics. The objectives of the study were to determine serum and tissue levels of SQ12 in turkey breeder hens to 14 days postinjection and to evaluate effects of SQ12 on reproductive status. Thirty photostimulated hens were housed in litter floor pens and provided with 14.5 hr of light per day in a curtain-sided facility. Six hens served as untreated controls. Twelve hens per treatment group received SQ injections in the neck with SQ12 at 11.4 (L dose group) or 22.7 mg/kg (H dose group) to assess low and high doses, respectively. Serum samples were obtained from each hen at predose and 6, 12, 24, 48, 72, 96, 168, 240, and 336 hr postinjection. All hens were euthanatized at 14 and 15 days postinjection. One-half of the hens in each treatment group were sampled (liver, lung, kidneys, and breast muscle) for tissue residue levels of OTC. The control group had no detectable OTC in serum or tissues at any sample collection time. There were no detectable serum levels of OTC in either treatment group prior to injection. The average serum concentrations of the L and H dose groups showed similar depletion curves although the H dose group was 42% higher at maximum concentration than the L group. Average tissue concentration of OTC for all tissues sampled from the H dose group was twice that of the L dose group. All tissue levels were below the OTC residue tolerance limit. SQ12 provided an extended source of OTC in serum of turkey breeder hens with no effect on reproductive status. SQ12 may provide for a novel treatment of bacterial infection in turkey breeder hens with longer lasting serum levels compared with other single injectable OTC products. RESUMEN. Nota de Investigacion-Un novedoso sistema de aplicacion de oxitetraciclina en parvadas de pavas reproductoras. Un novedoso producto (SQ12) de aplicaci6n subcutanea, a base de oxitetraciclina, ha sido disefiado para ser usado en explotaciones de producci6n animal. El SQ12 emplea esferas micro fluidas que contienen oxitetraciclina en forma cristalina, lo cual permite una liberaci6n mas prolongada de la oxitetraciclina en comparaci6n con otras formas inyectables del antibiotico. Los objetivos de este estudio fueron la determinaci6n de los niveles sericos y tisulares del SQ12 en las reproductoras hasta los 14 dias despues de la inyeccion, y la evaluacion de los efectos del producto sobre el aparato reproductivo de los animales. Treinta pavas foto estimuladas fueron mantenidas en corrales, sobre piso con yacija y expuestas a 14.5 horas de luz por dia en casetas con cortinas laterales. Seis de los animales sirvieron como grupo control no inoculado. El resto de la parvada fue dividida en grupos de 12 animales por tratamiento experimental, recibiendo inyecciones subcutaneas de SQ12 a raz6n de 11.4 mg/kg (grupo de dosis baja) o 22.7 mg/kg (grupo de dosis alta), con el fin de determinar los parametros mencionados a dosis bajas y altas del producto, respectivamente. Se tomaron muestras de sueros de cada ave antes del inicio de los tratamientos y a intervalos de 6, 12, 24, 48, 72, 96, 128, 240 y 336 dias despues de la inoculaci6n del producto. Todos los animales fueron

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D. K. Carveret al. sacrificadosa los 14 y 15 dias despues del inicio del tratamiento.La mitad de los animales en cada tratamientofueron usados parala obtenci6n de muestrasde tejido (higado, pulm6n, riiion y musculo pectoral)para determinarlos niveles de residuostisularesde oxitetraciclina. El grupo control no present6 niveles detectablesde oxitetraciclinaen las muestrasde suero o tejido en ninguna de las muestrastomadas. No se detectaron niveles sericos de oxitetraciclina en ninguno de los animales previo a la inoculacion del producto. Los promedios de las concentracionessericas en los grupos de dosis alta y baja mostraroncurvas similaresde eliminaci6n, aunque el grupo de dosis alta present6 un promedio de concentraci6nserica maxima (Cax) 42% mas alto que el del grupo de dosis baja. Los promedios de las concentraciones tisularesde oxitetraciclinaen todos los tejidos obtenidos del grupo de dosis alta fueron por lo menos dos veces mas altos que los del grupo de dosis baja. Todos los niveles de residuostisularesestuvieronpor debajo del nivel de toleranciamaximaresidualpermitidos para la oxitetraciclina.El producto SQ12 proporcionauna fuente de liberaci6nprolongada de oxitetraciclinaen el suero de las pavas reproductoras,sin presentarefectos adversosen el estado reproductivode los animales. El SQ12 puede proporcionaruna forma novedosa de tratamiento contra las enfermedadesde origen bacterianoen las parvadasde pavos reproductores, con niveles sericos maisprolongados, en comparaci6ncon otras preparacionesdel producto. Key words: turkey,antibiotic treatment,oxytetracycline,long acting Abbreviations:OTC = oxytetracycline;SQ = subcutaneous

fluidic spheresencasing oxytetracyclinecrystals(25 g OTC/100 ml). This formulationhas been shown to deliver a sustainedreleaseof the antibiotic in treated cattle over a much longer time framecomparedwith currently available injectable cattle antibiotics (K. Joyce, pers. comm.). Experimental design. This experimentwas conducted with 30 turkey breederhens concurrentlyinvolved in a nutrition study. One hen from each of 24 floor pens was selected at random to receive an injection of antibiotic. Six hens servedas controlsand received no antibiotic treatment.The hens averaged 25 lb each. Twelve hens received one low dose (L group) of 25 mg/lb body weight OTC (2.5 ml) via subcutaneous(SQ) injection in the neck. Twelvehens receivedone high dose (H group) of 50 mg/lb body weight OTC (5.0 ml) via SQ injection in the neck. Three control hens were commingled with L dose birds and three were comingled with H dose birds. Collection of serum. All hens, including controls, were sampled for blood serum at 0, 6, 12, 24, 48, 72, 96, 168, 240, and 336 hr postinjection via brachialvenipuncture (5 ml blood). Blood samples were allowed to clot at room temperatureand then centrifugedat 4 C for 15 min at 1500 rpm for serum harvest. Serum samples were held at -20 C and MATERIALSAND METHODS shipped to Colorado Animal Research Enterprises, Turkeys. Thirty photostimulated Nicholas large Inc., for bioavailabilityof OTC (1). white turkey breederhens were housed in litter floor Collection of tissues. All birds were euthanapens and provided with 14.5 hr of light per day in tized at 14-15 days postinjection. Samples of liver, a curtain-sidedfacility.The 70-wk-old hens had been lung, kidney, and breast muscle were collected from molted and were in the second lay cycle. The exper- six turkeysfrom each group and frozen at -20 C for iment was conducted 6-8 wk postlighting. shipment of Colorado Animal ResearchEnterprises, OTC. The OTC formulation used was SQ12 Inc., for tissue residue assay (2). Determination of bioavailability and tissue (Blue Ridge Pharmaceuticals,Inc., Greensboro,NC), which employs a patented delivery system of micro- residue. The bioavailabilityof OTC in serum was There has been an interest in the development and use of a long-acting oxytetracycline (OTC) injectable antibiotic product for the livestock industry, specifically to treat or prepare cattle for shipping. Long-acting OTC has been shown efficacious in treatment of turkeys experimentally infected with a virulent strain of Pasteurella multocida (4). Skeeles and coworkers (4,5) reported on a similar product for use in turkeys and noted its advantage of providing prolonged therapeutic blood levels after handling birds only once. More recently, another long-acting OTC product (SQ12) has been developed. The purpose of this study was to examine the usefulness of this product for breeder turkeys, specifically, bioavailability in serum over time and tissue residues of kidney, liver, breast muscle, and lungs 15 days after withdrawal. In addition, any affects on reproductive status in turkeys receiving this formulation were assessed.

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